The Neoadjuvant Net: A patient- and surgeon-friendly device to facilitate safe breast-conserving surgery in patients who underwent neoadjuvant treatment

The primary goal of the study was to describe an innovative and helpful tool in defining the minimal surgical margins necessary during breast-conserving surgery (BCS) after neoadjuvant treatment: the Neoadjuvant Net (NN). The secondary endpoint was to assess its usefulness in achieving postoperative disease-free margins and reducing Ipsilateral Breast Tumor Recurrences (IBRTs). The breast-conserving surgical technique together with the use of the Neoadjuvant Net is herein reported. Age, stage at diagnosis, clinical and pathological response, lymph node status, type of surgery, margin status, and incidence of local and distant recurrence were retrospectively analyzed. Seventy-five patients underwent BCS following medical treatment from 2000 to 2011. The majority of the patients had significant size reduction (63/75, 84%). Twenty-two had a complete clinical response but only 11 (11/75, 14.7%) showed a complete pathological response. Two patients (2/75, 2.67%) had infiltrated surgical margins. After a mean follow-up of seventy months, 3 patients (3/75, 4%) had IBRTs and 4 women had distant metastases (4/75, 5.34%). The NN is an easy-to-use, non-invasive instrument designed with the purpose of facilitating the surgeon's task of reducing infiltrated margins and IBTRs

c-myb Proto-Oncogene Is Expressed by Quiescent Scleroderma Fibroblasts and, Unlike B-myb Gene, Does Not Correlate With Proliferation

Systemic sclerosis (scleroderma) is characterized by excessive deposition of extracellular matrix constituents. Although it has been proposed that tissue fibrosis is due to increased fibroblast synthesis of various collagen polypeptides, there is some experimental evidence that patients with systemic sclerosis have a defect in the control of fibroblast growth. The myb family of genes includes, among others, the c-myb proto-oncogene and the structurally related gene, B-myb, which are both implicated in the regulation of differentiation and/or proliferation of hematopoietic and nonhematopoietic cells. To elucidate the molecular basis responsible for scleroderma fibroblast proliferation, we therefore elected to investigate the expression of c-myb and B-myb genes in scleroderma and control cells. Using the reverse transcriptase polymerase chain reaction technique, we detected c-myb transcripts in scleroderma skin fibroblasts rendered quiescent by serum deprivation. Under the game experimental conditions, c-myb message was not found in normal skin fibroblasts, but, after serum stimulation, c-myb RNA was clearly evident from 3 to 72h in both normal and pathologic cells. Treatment of these cells with c-myb antisense oligonucleotides caused downregulation of c-myb expression, and the inhibition of scleroderma fibroblast proliferation was 42%, whereas in normal fibroblasts the inhibition was weaker (22%). In contrast to c-myb, in normal and scleroderma fibroblasts the level of expression of B-myb correlated with cell proliferation assessed by cell count, and densitometric analysis showed that B-myb message was 1.5–5 times higher in most of pathologic cells studied. The antisense B-myb oligonucleotides had a weaker antiproliferative effect compared with antisense c-myb, inhibiting scleroderma and normal fibroblasts by 23% and 13%, respectively. These data suggest that the B-myb and c-myb genes may play a role in scleroderma fibroblast proliferation and function

Gene expression profile of human colon cancer cells treated with cross-reacting material 197, a diphtheria toxin non-toxic mutant

Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown anti-tumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory- immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAI1) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.Fil: Rivetti, S.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Lauriola, M.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Voltattorni, M.. Universidad de Bologna; ItaliaFil: Bianchini, Michele. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martini, D.. Universidad de Bologna; ItaliaFil: Ceccarelli, C.. Universidad de Bologna; ItaliaFil: Palmieri, A.. Università di Ferrara; ItaliaFil: Mattei, G.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Franchi, M.. Universidad de Bologna; ItaliaFil: Ugolini, G.. Universidad de Bologna; ItaliaFil: Rosati, G.. Universidad de Bologna; ItaliaFil: Montroni, I.. Universidad de Bologna; ItaliaFil: Taffurelli, M.. Universidad de Bologna; ItaliaFil: Solmi, Rosella. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; Italia. Universidad de Bologna; Itali

The Diverticular Disease Registry (DDR Trial) by the Advanced International Mini-Invasive Surgery Academy Clinical Research Network: Protocol for a Multicenter, Prospective Observational Study

Diverticular disease is an increasingly common issue, with a variety of clinical presentations and treatment options. However, very few prospective cohort studies explore outcomes between the different presentations and treatments. The Diverticular Disease Registry (DDR Trial) is a multicenter, prospective, observational cohort study on behalf of the Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network. The DDR Trial aims to investigate the short-term postoperative and long-term quality of life outcomes in patients undergoing surgery or medical treatments for diverticular disease. DDR Trial is open to participation by all tertiary-care hospitals. DDR Trial has been registered at ClinicalTriats.gou (NCT 04907383). Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on June 1 , 2021 and will end after 5 years of recruitment. All adult patients with imaging-proven colonic diverticular disease (i.e., symptomatic colonic diverticulosis including diverticular bleeding, diverticulitis, and Symptomatic Uncomplicated Diverticular Disease) will be included. The primary outcome of DDR Trial is quality of life assessment at 12-month according to the Gastrointestinal Quality of Life Index (GIQLI). The secondary outcome is 30-day postoperative outcomes according to the Clavien-Dindo classification. DDR Trial will significantly advance in identifying the optimal care for patients with diverticular disease by exploring outcomes of different presentations and treatments

Quality of Life in Older Adults After Major Cancer Surgery:The GOSAFE International Study

Abstract Background Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL. Methods GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale. Results Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P < .001). Domains showing improvement were pain and anxiety or depression. A Flemish Triage Risk Screening Tool score greater than or equal to 2 (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.13 to 2.21, P = .007), palliative surgery (OR = 2.14, 95% CI = 1.01 to 4.52, P = .046), postoperative complications (OR = 1.95, 95% CI = 1.19 to 3.18, P = .007) correlated with worsening QoL. Conclusions GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations

Use of fluorescence imaging and indocyanine green during colorectal surgery: Results of an intercontinental Delphi survey

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable

Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer

Purpose: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. Methods: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center’s adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. Conclusion: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. Clinical trial registration: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641)

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

Background: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Methods: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Results: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. Conclusion: This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cytomorphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death